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At least 19 recordsLinked to original sources
PubMed1992

Overexpression of Id protein inhibits the muscle differentiation program: in vivo association of Id with E2A proteins.

The helix-loop-helix (HLH) protein Id lacks the basic DNA-binding domain common to this class of proteins. In vitro experiments suggested that Id could associate tightly with two other HLH proteins encoded by the E2A gene, E12 and E47 (referred to here collectively as E proteins) and prevent their binding to a sequence present in the muscle creatine kinase (MCK) enhancer either as homo-oligomers or hetero-oligomers with MyoD. In this report we present evidence for the in vivo roles of Id and E proteins: (1) Id and E proteins co-fractionate and co-immunoprecipitate in whole-cell extracts prepared from myoblasts; (2) the loss of Id protein observed during the conversion of proliferating myoblasts into mature myotubes correlates with the formation of MyoD/E hetero-oligomeric complexes in whole-cell extracts (these complexes do not form when purified Id protein is added to the extracts); and (3) stable overexpression of Id mRNA and protein in the C2C12 muscle cell line inhibits differentiation in these cells 16 hr post-induction. The myotubes that do eventually form 48 hr post-induction have no detectable Id protein in the nucleus despite the persistence of exogenous Id mRNA. These data support a model in which Id can inhibit muscle cell differentiation by associating with E proteins and preventing them from forming active hetero-oligomeric complexes with the muscle determination gene products.

Animals↗
PubMed1987

Increased presence of common systemic lupus erythematosus (SLE) anti-DNA idiotypes (16/6 Id, 32/15 Id) is induced by procainamide.

Sixty-seven patients on treatment with procainamide were examined for the presence of two common idiotypes of anti-DNA antibodies (16/6 Id and 32/15 Id). These idiotypes have been shown previously to have clinical relevance in patients with systemic lupus erythematosus (SLE). An enzyme-linked immunosorbent assay (ELISA) with rabbit anti-Id antibodies revealed increased concentrations of the 16/6 Id and 32/15 Id in 25 (37%) and 16 (24%) patients, respectively. Five of eight patients with drug-induced lupus had elevated titers of both idiotypes. A high correlation (R = 0.56, P less than 0.001 for 16/6 Id) was found between Id levels and anti-single-stranded DNA (ssDNA) antibody titers and between 16/6 Id titers and antihistone antibodies (IgG, R = 0.43; IgM, R = 0.25). It seems that procainamide, a component known to be associated with drug-induced lupus, may induce an increased production of common anti-DNA idiotypes in apparently normal subjects.

Antibodies, Viral↗
PubMed1991

Identification of Staphylococcus species and subspecies with the MicroScan Pos ID and Rapid Pos ID panel systems.

The accuracies of the MicroScan Pos ID and Rapid Pos ID panel systems (Baxter Diagnostic Inc., MicroScan Division, West Sacramento, Calif.) were compared with each other and with the accuracies of conventional methods for the identification of 25 Staphylococcus species and 4 subspecies. Conventional methods included those used in the original descriptions of species and subspecies and DNA-DNA hybridization. The Pos ID panel uses a battery of 18 tests, and the Rapid Pos ID panel uses a battery of 42 tests for the identification of Staphylococcus species. The Pos ID panel has modified conventional and chromogenic tests that can be read after 15 to 48 h of incubation; the Rapid Pos ID panel has tests that use fluorogenic substrates or fluorometric indicators, and test results can be read after 2 h of incubation in the autoSCAN-W/A. Results indicated that both MicroScan systems had a high degree of congruence (greater than or equal to 90%) with conventional methods for the species S. capitis, S. aureus, S. auricularis, S. saprophyticus, S. cohnii, S. arlettae, S. carnosus, S. lentus, and S. sciuri and, in particular, the subspecies S. capitis subsp. capitis and S. cohnii subsp. cohnii. The Rapid Pos ID panel system also had greater than or equal to 90% congruence with conventional methods for S. epidermidis, S. caprae, S. warneri subsp. 2, S. xylosus, S. kloosii, and S. caseolyticus. For both MicroScan systems, congruence with conventional methods was 80 to 90% for S. haemolyticus subsp. 1, S. equorum, S. intermedius, and S. hyicus; and in addition, with the Rapid Pos ID panel system congruence was 80 to 89% for S. capitis subsp. ureolyticus, S. warneri subsp. 1, S. hominis, S. cohnii subsp. urealyticum, and S. simulans. The MicroScan systems identified a lower percentage (50 to 75%) of strains of S. lugdunensis, S. gallinarum, S. schleiferi, and S. chromogenes, although the addition of specific tests to the systems might increase the accuracy of identification significantly.

Autoanalysis↗
PubMed1991

Induction of systemic lupus erythematosus in naive mice with T-cell lines specific for human anti-DNA antibody SA-1 (16/6 Id+) and for mouse tuberculosis antibody TB/68 (16/6 Id+).

Previously we have shown the ability to induce experimental systemic lupus erythematosus (SLE) in naive mice with pathogenic antibodies carrying the 16/6 idiotype (Id) and with the T-cell line specific for the 16/6 Id. In the present study we established and characterized a series of T-cell clones that react against diverse autoantibodies carrying the 16/6 Id and show that they are capable of inducing a SLE-like disease in mice. The T-cell clones were generated from BALB/c mice immunized with the human mAb anti-DNA antibody (SA-1) and the mouse monoclonal anti-tuberculous Ab (TB/68), both carrying the 16/6 Id. The T-cell clones proliferated only in the presence of either human or mouse mAb carrying the 16/6 Id. All the T-cell clones were found to be of the helper type (L3T4) and were H-2 restricted in their function. The injection of the clones to BALB/c mice resulted in serological findings (e.g., anti-DNA, anti-Sm), clinical manifestations (e.g., proteinuria, low white blood cell counts, increased erythrocyte sedimentation rate), and renal insult typical of SLE disease. Our data support the role attributed to pathogenic idiotypes in SLE on the one hand and that played by cellular immunity on the other. The mechanism by which Id-specific T-helper cells may induce SLE is currently not clear. The immunogenicity of the T-cell receptor (anti-16/6) and the cells themselves acting as effector/helper cells, thus leading to damage, may play a role in initiating a chain of events that ends in the production of a panoply of autoantibodies, some of which may also have a regulatory function.

Animals↗
PubMed1992

[Comparative study of antibody identification in the gel centrifugation test (ID Microtyping System), solid phase antiglobulin test (Solidscreen Capture R, Ready ID) and tube test].

The gel centrifugation test (ID Microtyping System)--a new method for antibody screening--was compared with solid phase systems (Solidscreen, Capture R, Ready ID) and the conventional tube test. 141 different antibodies were tested and the results were compared. The ID Microtyping System identified 138 (98%) of all antibodies, the tube test 110 (78%), Capture R 86 (61%), Ready ID 79 (56%) and Solidscreen 75 (53%). The results in identification of all antibodies except cold agglutinins (n = 107) were: in the ID Microtyping System 98% (105), tube test 76% (82), Capture R 70% (75), Ready ID 68% (73) and Solidscreen 61% (65).

Antibody Specificity↗
PubMed1985

Molecular characterization of antibodies bearing Id-460. II. Molecular basis for Id-460 expression.

Id-460+ immunoglobulins can be induced in vivo by immunization with dinitrophenyl (DNP) or P. pneumotropica and form two nonoverlapping groups of antibodies with respect to antigen binding specificity. In this study, using Id-460+ antibodies of differing antigen binding specificities, we compared on the molecular genetic level the five gene segment combinations (VH, DH, JH, VL, and JL) that encode the variable regions of these idiotype-positive immunoglobulins. The Id-460 determinant appears to be a conformational or combinatorial determinant encoded by VH460 and VK1 crosshybridizing genes. DH, JH, and JK gene segments appear to have no measurable effect upon expression of Id-460. Finally, antigen binding specificity does not appear to simply localize to any particular gene segment but may in part be the result of somatic mutation and/or VDJH junctional sequences, whose length correlates roughly with antigen binding specificity.

Amino Acid Sequence↗
PubMed1991

Comparison of API Rapid Strep, Baxter MicroScan Rapid Pos ID Panel, BBL Minitek Differential Identification System, IDS RapID STR System, and Vitek GPI to conventional biochemical tests for identification of viridans streptococci.

Viridans group streptococci (36 stock strains and 167 single patient blood culture isolates) were assessed using API Rapid Strep, Baxter MicroScan Rapid Pos ID Panel, BBL Minitek Differential Identification System, IDS RapID STR System, and Vitek GPI methods. Identification data obtained with these systems were compared with those indicated by conventional biochemical procedures. API, Baxter MicroScan, BBL, IDS, and Vitek corresponded with conventional biochemical identification in 74%, 66%, 65%, 50%, and 61% of the isolates, respectively; using recommended supplemental tests, agreement was augmented in 9%, 11%, 20%, 11%, and 21% of the isolates, respectively. Disagreement with conventional biochemical methods occurred in 14%, 17%, 14%, 32%, and 10% of the commercial techniques, respectively; no identification was possible in 2%, 5%, fewer than 1%, 6%, and 8% of specimens, respectively. BBL, API, and Baxter MicroScan systems provided the most reliable rapid identification, although supplemental testing often was required. Until a higher percentage of correct identification data can be obtained without supplemental procedures, conventional biochemical techniques will remain the methods of choice for identification of viridans streptococci.

Bacteriological Techniques↗
PubMed1977

Regulatory substances produced by lymphocytes. V. Production of inhibitor of DNA synthesis (IDS) by proliferating T lymphocytes.

The conditions neccessary for production of inhibitor of DNA synthesis (IDS) by rat lymphocytes were investigated. In concanavalin A (Con A)-stimulated lymph node cell (LNC) cultures, IDS production was not detected in the culture supernatant during the first 24 hr, and it increased gradually after that to reach a maximum at 3 to 4 days. When the cells were pretreated with mitomycin C, IDS was not produced, suggesting that DNA synthesis of LNC or a LNC subpopulation is necessary for IDS production. In contrast, Con A-stimulated spleen cells priduced a high level of IDS within 24 hr, and its production fell off sharply thereafter. Con A-stimulated rat thymocytes also produced IDS reaching a maximum at 2 to 3 dyas. However, thymus cells from rats treated with hydrocortisone 48 hr previously did not produce IDS. This finding implies that cortisol-sensitive (cortical) thymocytes are capable of producing IDS and cortisol-resistant (medullary) thymocytes are not. IDS production by lymphoblasts was proportional to cell number and unaffected eith by cell density (1 to 10 x 106/ml) or by the concomitant presence of normal cells from spleen, lymph node, or thymus. Thus Con A-stimulated cells, after becoming blasts, appear to produce IDS automatically wihtout affecting or being affected by other cells. Both spleen and thymus cells from rats injected with a large dose of antigen (ovalbumin, 100 mg, i.p.) 24 hr in advance produced substantial amounts of IDS in culture within 24 hr in the absence of mitogen or additional antigen, but not the cells from rats injected with an immunizing dose (1 mg) of the same antigen. The cells producing IDS in the spleen were shown to be adherent to glass wool, and those in the thymus were partially so. IDS production by antigen-stimulated spleen cells was abrogated by injecting rats with bromodexyuridine (BUdR) at 0 and 12 hr after the ovalbumin. These findings suggest that a subpopulation ofadherent spleen cells (possibly resembling cortical thymocytes), which begins to proliferate within a few hours after a large dose of systemic antigen, produces IDS. This may account for increased nonspecific suppressor activity observed at the same time.

Animals↗
PubMed1992

A human Id-like helix-loop-helix protein expressed during early development.

The interaction of helix-loop-helix (HLH) proteins is known to regulate the differentiation of several different tissues, including mammalian muscle and the insect peripheral nervous system. In myoblasts, the products of myogenic HLH genes such as MyoD and ubiquitous HLH proteins such as E12 are present at constant levels throughout development. An E12 monomer and a MyoD monomer form a DNA binding heterodimer that activates muscle-specific genes. These two proteins are unable to dimerize in proliferating myoblasts because a negative regulator HLH protein, Id, is present. We now report the sequence and structure of a human HLH gene related to Id, which has been designated Id-2. Two prominent Id-2 RNA molecules of 2.5 and 1.3 kilobases were found in a number of different human normal and neoplastic tissues. We believe the larger RNA is a precursor of the 1.3-kilobase mRNA that encodes an Id-2 protein of 134 amino acids. The HLH region of the Id-2 protein is 90% homologous to that of myogenic Id, but the homology is much less extensive outside the HLH region. The Id-2 gene is highly expressed during early fetal development in several tissues, including those of the central nervous system, but is not expressed in the corresponding mature tissues. Id-2 expression is modulated in association with retinoic acid-induced ganglionic differentiation of the neuroblastoma cell line SMS-KCNR. These findings suggest that Id-2 is an inhibitor of tissue-specific gene expression, although its distinctive pattern of expression during development suggests a role different from that of Id.

Amino Acid Sequence↗
PubMed1975

Electrophysiological and behavioral effects of 1-methyl-5-(o-fluorophenyl)-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-one (ID-540) in cats and rabbits.

Effects of ID-540 (1-methyl-5-(o-fluorophenyl)-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-one) on the central nervous system were evaluated electrophysiologically and behaviorally in cats and rabbits. The reference compound used was diazepam. 1. ID-540 as well as diazepam produced muscle relaxation, grooming, facilitation of appetite and suppression of defensive behaviors. ID-540 made the animals lie on their side during sleep, but diazepam did not. 2. Though more effectively inducing an increase in fast activity and a decrease in frequency of hippocampal theta-waves than diazepam, ID-540 scarcely affected the amplitude of subcortical EEG (hippocampus, amygdala and hypothalamus), which diazepam decreased in cats. 3. ID-540 and diazepam increased the waking phase and decreased the paradoxical sleep phase. 4. ID-540 and diazepam at a dose of 1 mg/kg decreased the duration of amygdala after-discharge for 1 h in cats. Diazepam increased the duration of the after-discharge after it had been decreased, but ID-540 did not. ID-540 did not affect the duration of hippocampal after-discharge whereas diazepam prolonged it. 5. ID-540 depressed more effectively the hippocampal arousal response to stimulation of the ventro-medial hypothalamus than did diazepam in rabbits. 6. ID-540 depressed amygdalo-hippocampal evoked potential in cats. 7. ID-540 did not affect norepinephrine-induced pressor response but reduced hypothalamic pressor response in cats.

Animals↗
PubMed1987

Monoclonal anti-Id antibodies react with varying proportions of human B lineage cells.

Monoclonal antibodies to idiotypic determinants are being used with increasing frequency for analysis and treatment of B cell malignancies. In the present study we have compared the idiotypic specificities of a panel of 39 mouse monoclonal anti-idiotype (anti-Id) antibodies developed against 16 monoclonal human immunoglobulins (Ig). The Id cross-reactivities of these antibodies with Ig products of normal and abnormal B cells were examined by immunofluorescence and immunochemical methods. The reactivity patterns of these anti-Id antibodies with a normal population of plasma cells were highly variable in the immunofluorescence assay. Six were reactive with 2 to 10% of normal plasma cells, 30 with 0.1 to 2% of plasma cells, and three with less than 0.1% of plasma cells from blood, bone marrow, spleen, or tonsils. These reactivity patterns were relatively consistent among samples from 23 Caucasian, black, and Oriental adults. Although the reactivities of most anti-Id antibodies in the panel were not restricted to a particular Ig isotype, several were preferentially reactive with a particular heavy or light chain isotype: one IgM-, two IgA-, two kappa-, and three lambda-restricted antibodies. The immunofluorescence data was confirmed by biosynthetic analysis of Id+ molecules produced by a normal plasma cell population. When the reactivity of this panel of anti-Id antibodies with nonhomologous B cell neoplasms was examined, seven of 30 myelomas or leukemia-derived products and one of nine B cell leukemias or lymphomas without paraproteins were found to be cross-reactive with one or two of the anti-Id antibodies. Although clearly significant, the cross-reactivity between the Id of these paraproteins appeared to be of lower affinity than the reactivity of the homologous Id with their respective anti-Id antibodies. The results reveal a remarkable diversity in the specificities of monoclonal antibodies classified by conventional criteria as anti-Id antibodies, and indicate the potential usefulness of a panel of antibodies for analyzing clonal diversity in normal and abnormal B cell development.

Adult↗
PubMed1992

Id expression during mouse development: a role in morphogenesis.

We have characterized the spatial and temporal pattern of Id transcription during mouse embryogenesis. The Id gene encodes a helix-loop-helix (HLH) protein which can heterodimerize with the ubiquitously expressed HLH protein products of the E2A gene, and prevent them from binding DNA either alone or as a heterodimer with tissue specific HLH transcription factors such as the muscle determination gene, MyoD1 (Benezra et al., 1990: Cell 61:49-59). Since Id has been shown to be down-regulated during induced differentiation in several cell lines, it has been postulated that Id plays a general inhibitory role in cell differentiation (Benezra et al., 1990). In situ analysis of Id mRNA expression in the mouse embryo was performed in order to determine whether the pattern of Id expression is consistent with this postulate. A detailed study throughout the entirety of mouse postimplantation development reveals that Id is expressed upon gastrulation at very high levels in almost all regions of the mouse embryo and expression declines as embryogenesis proceeds. In skeletal muscle, in which the inhibitory action of Id has been established in tissue culture models (Benezra et al., 1990), Id and the HLH myogenic factors are expressed in a mutually exclusive manner suggesting that myogenic precursors do not express both types of HLH gene products. In addition, Id colocalizes both spatially and temporally with Hox-7.1, a murine homeobox gene which is associated with regions of high cell proliferation and positional fate assignment.

Animals↗
PubMed1986

The Inventory for Depressive Symptomatology (IDS): preliminary findings.

The Inventory for Depressive Symptomatology (IDS) is a new measure of depressive signs and symptoms. Both self-report and clinician-rated versions are under development. The IDS-SR (self-report) was completed by 289 patients, 285 of whom were outpatients. Unipolar major depression (n = 174), bipolar disorder (n = 44), euthymic (S/P unipolar or bipolar) depression (n = 33), and other psychiatric disorders (n = 38) were included. The IDS-SR had good internal reliability (coefficient alpha = 0.85), and significantly correlated with both the Hamilton Rating Scale for Depression (HRSD) (r = 0.67) and the Beck Depression Inventory (BDI) (r = 0.78). The clinician-rated IDS (IDS-C) was administered to 82 outpatients (75 with unipolar or bipolar disorder, 5 with other psychiatric disorders, and 2 euthymic (S/P unipolar) depressions). Coefficient alpha (0.88) suggested strong internal consistency. The IDS-C correlated highly with both the HRSD (r = 0.92) and the BDI (r = 0.61). Discriminant and factor analyses provided evidence for construct validity for both the IDS-C and IDS-SR. Both scales significantly differentiated endogenous from nonendogenous depression defined by Research Diagnostic Criteria (RDC). Factor structures for the IDS-SR revealed four factors: mood/cognition, anxiety, selected endogenous symptoms, and hyperphagia-hypersomnia. The IDS appears applicable to both inpatients and outpatients with endogenous, atypical, and nonendogenous major depression, and may have utility with dysthymics.

Adult↗
PubMed1976

[Effects of l-methyl-5-(O-fluorophenyl)-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-One (ID-540) on operant behavior in rats].

Effects of ID-540, a new benzodiazepine derivative, on operant behavior were studied and compared with those of diazepam in rats for the purpose of determining the characteristics on behavioral pharmacology. Four schedules used were as follows: Fixed interval (FI-60sec) of food reinforcement and differential food reinforcement of low rate (DRL20sec) for positively reinforced behavior, Sidman-type avoidance response for negatively reinforced behavior and conflict behavior induced by simultaneously rewarding with food and punishing with electric shock. In the experiments on FI-60sec schedule, the responses at the early stage (0 approximately 30 min after administration of the drug) were increased by both ID-540 and diazepam at lower doses (0.5 approximately 4 mg/kg p.o.), but inhibited at higher doses (8 approximately 32 mg/kg p.o.). The effect of ID-540 lasted longer than that of diazepam. In the experiments on DRL20sec schedule, neither drug accelerated the responses, but decreased the lever-press response and total number of reinforcements at higher doses (4 mg/kg or more) showing the disturbance of discrimination on time. In Sidman-type avoidance responses, ID-540 did not show any inhibitory effect, thus a neuroleptic-like effect of ID-540 was not demonstrated. In experiments on FI-60sec and Sidman-type avoidance schedules, the effect of ID-540 was not changed by a consecutive administration for 10 days. Conflict behavior is considered to resemble the anxiety states in humans, and in related experiments, ID-540 increased the lever-press response which delivered a food-pellet and an electric shock simultaneously at a dose of 0.0625 mg/kg (i.p.). Change in other behavior was not observed at this dose level. Maximum effect of ID-540 was observed at a dose of 0.5 mg/kg (i.p.). Maximum effect of diazepam on conflict behavior was seen at a dose of 4 mg/kg (i.p.). The potency of ID-540 on conflict behavior was estimated to be about 8 times that of diazepam.

Animals↗
PubMed1992

Expression of a chimeric helix-loop-helix gene, Id-SCL, in K562 human leukemic cells is associated with nuclear segmentation.

We have designed a chimeric gene, Id-SCL, in which the 3' helix-loop-helix encoding portion of the presumptive oncogene SCL/tal is joined to the 5' coding portion of Id, an inhibitory helix-loop-helix gene. The predicted protein product of this chimeric gene contains the helix-loop-helix dimerization domain of SCL/tal, but, lacking a basic DNA binding domain, is predicted to have the inhibitory function of the Id product. Expression of the Id-SCL fusion gene in stably transfected K562 cells reproducibly resulted in nuclear segmentation and depressed growth rates; both of these phenotypic effects demonstrated a dosage dependence on the levels of Id-SCL mRNA and protein expressed in the various clones. Electron microscopy of cells expressing high levels of Id-SCL mRNA showed a significant increase in cytoplasmic perinuclear thin filaments and diminution of marginal heterochromatin in the nuclei. No other changes in hematopoietic differentiation status were observed in association with Id-SCL expression. Expression of intact Id and SCL/tal genes, as well as deletion mutants of Id and SCL/tal, independently transfected into K562 cells, indicated that the nuclear segmentation effect is dependent on the presence of a protein possessing a helix-loop-helix domain but lacking a basic domain. Our studies suggest that the balance of transcriptional inhibitory and stimulatory helix-loop-helix proteins in cells may be important determinants of proliferation and of structural organization within cells.

Amino Acid Sequence↗